Biliary atresia, the most common infantile liver disease, is characterized by occlusion of the entire biliary tree. The etiology of biliary atresia s unknown, but a developmental anomaly of the biliary system or the progressive destruction of the biliary system due to viral infection or environmental factors have been proposed to responsible for the disease. In order to understand the genetic factors that contribute to the pathogenesis of biliary atresia, we undertook forward genetic and chemical screens to identify previously unappreciated genes and pathways that are responsible for biliary system formation in zebrafish. We will investigate the molecular mechanisms underlying biliary atresia-like phenotypes in zebrafish by using our innovative computational algorithms to quantify subtle difference in three-dimensional biliary branching patterns. Building on this work, we will then extend our studies to human biliary atresia patient samples to investigate the pathology. Successful execution of this collaborative scientific endeavor promises to develop important new scientific insights into biliary system formation, and may have profound implications for our understanding of the pathology of biliary atresia.